Dataset Information

Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-? peptide.

ABSTRACT: ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-? peptide (A?). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamically favorable binding at the putative sterol-binding site, and this was greater than for cholesterol. Additionally, unbiased docking also showed A? binding at this site. Using a novel Abcg4-deficient mouse model, we show that Abcg4 was able to export A? and desmosterol at the BBB level and these processes could be inhibited by probucol and L-thyroxine. Our assay also showed that desmosterol antagonized the export of A?, presumably as both bind at the sterol-binding site on Abcg4. We show for the first time that Abcg4 may function in vivo to export A? at the BBB, in a process that can be antagonized by its putative natural ligand, desmosterol (and possibly cholesterol).

SUBMITTER: Dodacki A

PROVIDER: S-EPMC5645361 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide.

Dodacki Agnès A Wortman Matthew M Saubaméa Bruno B Chasseigneaux Stéphanie S Nicolic Sophie S Prince Nathalie N Lochus Murielle M Raveu Anne-Laure AL Declèves Xavier X Scherrmann Jean-Michel JM Patel Shailendra B SB Bourasset Fanchon F

Scientific reports 20171017 1

ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro, to participate in the cellular efflux of desmosterol and amyloid-β peptide (Aβ). ABCG4 is highly expressed in the brain, but its localization and function at the blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR and confocal imaging that mouse Abcg4 is expressed in the brain capillary endothelial cells. Modelling studies of the Abcg4 dimer suggested that desmosterol showed thermodynamic ...[more]

PMID: 29042617

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Dataset Information

Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-? peptide.

Publications

Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide.

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